This project provides a carefully organized training program and a focused research project that will enable the candidate to pursue a career as an independent pediatric physician-scientist. Training/Environment: The candidate has previous basic science training as a graduate student while enrolled in a combined M.D./ Ph.D. program, and has subsequently completed residency and subspecialty training. The program in this application involves a new field for the candidate, focusing on the basic mechanisms of early cardiac development. The scientific mentor and laboratory provide a complete background in embryology and developmental biology, in both the mouse and chick model systems. The academic environment provides important seminar series and symposia, and an advisory committee has been established to mentor the candidate. Research Plan: Epithelial-mesenchymal interactions and transformations play pivotal roles in morphogenesis of the heart in higher vertebrates. Epithelial-mesenchymal transformation of endocardial cells during the formation of the endocardial cushions is essential for normal septation and valvulogenesis, while transformation of epicardial cells is critical for development of the coronary vasculature. Furthermore, interactions between the developing epicardium and the myocardium are essential for normal myocardial development. Sox11, a member of the SRY family of transcription factors, is thought to be involved in epithelial-mesenchymal inductive processes during embryogenesis. The studies in this proposal test the hypothesis that Sox11 is involved in signaling between the endocardium and epicardium and subjacent mesenchyme during cardiac morphogenesis. Preliminary data shows that Sox11 is expressed in the endocardium and proepicardium during critical periods of epithelial-mesenchymal transformation and induction in the developing heart. In an effort to delineate the role of Sox11 in cardiac development, we propose to: 1) delineate Sox11 expression in the heart during critical stage of cardiac development; 2) examine the function of Sox11 in development of the endocardial cushions in = embryos; 3) examine the function of Sox11 in development of the epicardium; 4) create endothelial- and epicardial-specific null mutations of Sox11 to determine the requirement for Sox11 for cardiac development in the mouse. This work will provide important insight into the basic processes of cardiac development.